Gastrointestinal Stromal Tumors, Intramural Leiomyomas, and Leiomyosarcomas in the Rectum and Anus

Abstract

Gastrointestinal stromal tumors (GISTs), the specific KIT-positive mesenchymal tumors of the gastrointestinal tract, have been sporadically reported in the rectum, but there are few clinicopathologic series. In this study we analyzed the clinicopathologic features of 133 anorectal GISTs, 3 intramural leiomyomas (LMs), and 8 leiomyosarcomas (LMSs) from the files of the Armed Forces Institute of Pathology and the Haartman Institute of the University of Helsinki. Ninety-six GISTs were documented as KIT-positive and three additional ones as CD34-positive. Thirty-four tumors were included by their histologic similarity to KIT- or CD34-positive cases. GIST-specific c-kit gene mutations, mostly in exon 11, were documented in 18 of 29 cases (62%). The GISTs occurred in adults with the age range of 17-90 years (median 60 years) with a significant male predominance (71%). The tumors ranged from small asymptomatic intramural nodules to large masses that bulged into pelvis causing pain, rectal bleeding, or obstruction. They were mostly highly cellular spindle cell tumors; four tumors had an epithelioid morphology. The tumors coexpressed CD34 and KIT and were rarely positive for smooth muscle actin or desmin and never for S-100 protein. Seventy percent of patients with tumors >5 cm with more than 5 mitoses/50 high power fields (HPF) (n = 31) died of disease, whereas only one tumor <2 cm with <5 mitoses/50 HPF (n = 21) recurred and none caused death. Long latency was common between primary operation and recurrences and metastases; either one occurred in 60 of 111 patients with follow-up (54%). Distant metastases were in the liver, bones, and lungs. Three benign actin- and desmin-positive and KIT-negative intramural LMs, similar to those seen in the esophagus, were identified. There were eight LMSs, six of which formed a polypoid intraluminal mass and were actin-positive and KIT-negative. Despite high mitotic counts, only one LMS patient died of disease. A great majority of rectal smooth muscle and stromal tumors are GISTs, which have a spectrum from minimal indolent tumors to overt sarcomas. Intramural LMs are exceptional, and true LMSs are rare, and similar to colonic ones, often present as intraluminal polypoid masses that appear to have a better prognosis than GISTs with similar mitotic rates.

Quantitative immunohistochemical expression of c Kit in breast carcinomas is predictive of patients' outcome

“…In particular, for the triple-negative (ER-PgR-HERnegative) tumours, this deeper molecular insight into tumour characterisation should allow new targets for tailored therapies to be identified. In this regard, the inhibition of c Kit gene expression by imatinib (STI 571, Glivec), which was initially shown to be effective in the treatment of chronic myeloid leukaemia (Kantarjian et al, 2002), has more recently been found effective also against c Kit-positive gastrointestinal stroma tumours (GIST) (Miettinen et al, 2001), suggesting that other c Kit-positive tumours, in particular breast carcinomas, may respond to imatinib therapy.…”

Stage and histological grade of gastrointestinal stromal tumors based on a new approach are strongly associated with clinical behaviors

“…Mucosal infiltration was registered when tumor cells infiltrated inside the normal epithelial layers 23,27,28 ( Figure 5). Invasion of fat 29,30 ( Figure 6) or nerve tissues (Figure 7), vascular infiltration or tumor emboli 31 ( Figure 8) and lymph node metastasis were all recorded. Pathological changes in the tumor stromal structures (cystic, hemorrhagic) were also recorded.…”

Primary cilia in gastrointestinal stromal tumors

“…GIST are usually found in the stomach (60%) and small intestine (30%), but may also appear anywhere in the gastrointestinal tract and the intra-abdominal soft tissues. Tumor size and mitotic count are the primary prognostic parameters for GIST which can show spindle cell or epithelioid morphology [6]. Based on the results of prospective trials demonstrating disease control in the majority of the patients, with median survival in responding patients being around 6 years [7,8], imatinib, a tyrosine kinase inhibitor, was established as the therapy of choice for patients with metastatic inoperable GIST [9].…”